The principal objective of the proposed research is to assess the effect of humoral and select cell-mediated immune responses to human sperm antigens in human reproduction. The possibility that immunologic mechanisms can result in infertility has long been recognized, and several qualitative assays are available for detecting antisperm antibodies. Partially due to imprecision, these assays have had only limited clinical utility in the diagnosis and management of infertility, and have been sub-optimal investigative tools. Our first task is to enhance our capacity to identify and quantitate antisperm antibodies of the major immunoglobulin classes in human plasma and reproductive tract fluids. This will be accomplished with our recently established quantitative liquid-phase radioimmunoassay, as well as a solid-phase radioimunoassay and enzyme-linked immunosorbent assay which are currently being developed. These assays will be applied to the study of antisperm antibodies in fertile, infertile, and post-vasectomy patients. The biologic activities of these antibodies will be determined using several in vitro tests of reproductive function, including the human sperm/zona-free egg assay, the bovine cervical mucus penetration and measurements of sperm motility. The effect of several therapeutic modalities such as elution of antibodies from sperm and pharmacologic immunosuppressive therapy will be studied with regard both to alteration in the level of antisperm antibody and also the number of subsequent pregnancies. Immunoprecipitation techniques will be used to isolate sperm surface antigens, using antibodies from infertile patients' plasmas and monoclonal antibodies. The role of complement in mediating damage to sperm will be evaluated by directly assaying complement components on sperm surface in plasma and reproductive secretions from patients with antibody-mediated infertility. Complement/sperm interaction will be studied following activation of the alternative and classic complement pathways by quantitative immunochemical and functional techniques. Macrophage/sperm interactions will be assessed. Macrophage subsets will be isolated in an attempt to identify which subpopulation modulate sperm function. These studies should provide insight into the nature of the interactions between antibodies, complement macrophage and sperm, define the pathophysiology of immunologic infertility, and lead to rational approaches to therapy.